Search

Background: Major societal guidelines recommend a 5-day stop interval before cardiac surgery for patients with acute coronary syndrome receiving clopidogrel. Yet, many such patients present with high acuity, generating surgeon inclination toward use of shorter stop intervals. Thus, this study aimed to determine the impact of the duration and timing of the interval of clopidogrel cessation on adverse bleeding events. Methods: Patients who underwent cardiac surgery between 2009 and 2016 at a tertiary-care centre were included in this retrospective cohort study. Multivariable logistic regression models adjusted for clopidogrel stop interval, age, urgency of procedure, and procedure type were used to quantify the effect of clinically relevant baseline demographic characteristics on incidence of massive transfusion as well as hemorrhagic complication outcomes. Results: A total of 5748 patients underwent cardiac surgery. In this cohort, 1743 patients (30.3%) received clopidogrel preoperatively, and 884 (50.7%) of these patients discontinued clopidogrel 5 days before presenting to the operating room. The administration of clopidogrel 1-2 days before surgery (odds ratio 1.97; 95% confidence interval: 1.18 to 3.29) was an independent predictor for massive transfusions and hemorrhagic complications (odds ratio 1.85; 95% confidence interval: 1.01 to 3.37). The 3-4 day group did not have an increased risk of major bleeding complications. The risk for both massive transfusions and hemorrhagic complications also increased with the urgency and complexity of surgery. Conclusion: A clopidogrel stop interval of 3-4 days preoperatively was not associated with an increased risk for major bleeding complications. Résumé: Introduction: Les grandes lignes directrices sociétales recommandent une interruption de cinq jours avant l’intervention chirurgicale du cœur des patients atteints d’un syndrome coronarien aigu qui prennent du clopidogrel. Toutefois, comme il s’agit pour plusieurs d’entre eux de patients de haute acuité, le chirurgien penche vers l’utilisation d’une interruption plus courte. Par conséquent, la présente étude avait pour objectif de déterminer les conséquences de la durée et du moment de la cessation du clopidogrel sur les événements hémorragiques indésirables. Méthodes: La présente étude de cohorte rétrospective portait sur les patients qui avaient subi une intervention chirurgicale au cœur entre 2009 et 2016 dans un centre de soins tertiaires. Nous avons utilisé les modèles multivariés de régression logistique ajustés à l’interruption du clopidogrel, à l’âge, à l’urgence de l’intervention chirurgicale et au type d’intervention chirurgicale pour quantifier les effets des caractéristiques démographiques initiales cliniquement pertinentes sur la fréquence des transfusions massives ainsi que sur les issues des complications hémorragiques. Résultats: Un total de 5 748 patients ont subi une intervention chirurgicale au cœur. Dans cette cohorte, parmi les 1 743 patients (30,3 %) qui avaient reçu du clopidogrel avant l’opération, 884 (50,7 %) avaient cessé le clopidogrel cinq jours avant leur admission à la salle d’opération. L’administration du clopidogrel un à deux jours avant l’intervention chirurgicale (ratio d’incidence approché 1,97; intervalle de confiance [IC] à 95 % : de 1,18 à 3,29) était un prédicteur indépendant des transfusions massives et des complications hémorragiques (ratio d’incidence approché 1,85; [IC] à 95 % : de 1,01 à 3,37). Le groupe de l’interruption de trois à quatre jours n’a pas montré de risque accru de complications hémorragiques graves. Le risque de transfusions massives et de complications hémorragiques a aussi contribué à l’augmentation de l’urgence et de la complexité de l’intervention chirurgicale. Conclusion: Une interruption du clopidogrel de trois à quatre jours avant l’opération n’a pas été associée à un risque accru de complications hémorragiques graves.

BACKGROUND The Carpentier-Edwards Perimount valves have a proven track record in aortic valve replacement: good durability, hemodynamic performance, rates of survival, and low rates of valve-related complications and prosthesis-patient mismatch. The St. Jude Medical Trifecta is a newer valve that has shown comparable early and midterm outcomes. Studies show reoperation rates of Trifecta are comparable with Perimount valves, with a few recent studies bringing into focus early structural valve deterioration (SVD), and increased midterm SVD in younger patients. Given that midterm data for Trifecta is still sparse, we wanted to confirm the early low reoperation rates of Trifecta persist over time compared with Perimount. METHODS The Maritime Heart Centre Database was searched for AVR between 2011 and 2016, inclusive. The primary endpoint of the study was all-cause reoperation rate. RESULTS In total, 711 Perimount and 453 Trifecta implantations were included. The reoperation hazards were determined for age: 0.96 (0.92-0.99; p = .02), female (vs. male): 0.35 (0.08-1.53; p = .16), smoker (vs. nonsmoker): 2.44 (0.85-7.02; p = .1), and Trifecta (vs. Perimount): 2.68 (0.97-7.39; p = .06). Kaplan-Meier survival analysis in subgroups-age

Cancer causes substantial emotional and psychosocial distress, which may be exacerbated by delays in treatment. The COVID-19 pandemic has resulted in increased wait times for many patients with cancer. In this study, the psychosocial distress associated with waiting for cancer surgery during the pandemic was investigated. This cross-sectional, convergent mixed-methods study included patients with lower priority disease during the first wave of COVID-19 at an academic, tertiary care hospital in eastern Canada. Participants underwent semi-structured interviews and completed two questionnaires: Hospital Anxiety and Depression Scale (HADS) and Perceived Stress Scale (PSS). Qualitative analysis was completed through a thematic analysis approach, with integration achieved through triangulation. Fourteen participants were recruited, with cancer sites including thyroid, kidney, breast, prostate, and a gynecological disorder. Increased anxiety symptoms were found in 36% of patients and depressive symptoms in 14%. Similarly, 64% of patients experienced moderate or high stress. Six key themes were identified, including uncertainty, life changes, coping strategies, communication, experience, and health services. Participants discussed substantial distress associated with lifestyle changes and uncertain treatment timelines. Participants identified quality communication with their healthcare team and individualized coping strategies as being partially protective against such symptoms. Delays in surgery for patients with cancer during the COVID-19 pandemic resulted in extensive psychosocial distress. Patients may be able to mitigate these symptoms partially through various coping mechanisms and improved communication with their healthcare teams.

While extracorporeal membrane oxygenation (ECMO) is an effective method of oxygenation for patients with respiratory failure, further refinement of its incorporation into airway guidelines is needed. We present a case of severe glottic stenosis from advanced thyroid carcinoma in which gas exchange was facilitated by veno-arterial ECMO prior to achieving a definitive airway. We also conducted a systematic review of the MEDLINE, EMBASE, CINAHL, and Web of Science databases, using the keywords "airway/ tracheal obstruction", "anesthesia", "extracorporeal", and "cardiopulmonary bypass" to identify reports where ECMO was initiated as the a priori method of oxygenation during difficult airway management.Thirty-six papers were retrieved discussing the use of ECMO or cardiopulmonary bypass (CPB) for the management of critical airway obstruction. Forty-five patients underwent pre-induction of anesthesia institution of CPB or ECMO for airway obstruction. The patients presenting with critical airway obstruction had a range of airway pathologies with tracheal tumours (31%), tracheal stenosis (20%), and head and neck cancers (20%) being the most common. All cases reported a favourable patient outcome with all patients surviving to hospital discharge without significant complications.While most practitioners are familiar with the fundamental airway techniques of bag-mask ventilation, supraglottic airway use, tracheal intubation, and front-of-neck airway access for oxygenation, these techniques have limitations in managing patients with pre-existing severe airway obstruction. The use of ECMO should be considered in patients with severe (or near-complete) airway obstruction secondary to anterior neck or tracheal disease. This approach can provide essential tissue oxygenation while attempts to secure a definitive airway are carried out in a controlled environment.

Background Delirium is a temporary mental disorder that occasionally affects patients undergoing surgery, especially cardiac surgery. It is strongly associated with major adverse events, which in turn leads to increased cost and poor outcomes (eg, need for nursing home due to cognitive impairment, stroke, and death). The ability to foresee patients at risk of delirium will guide the timely initiation of multimodal preventive interventions, which will aid in reducing the burden and negative consequences associated with delirium. Several studies have focused on the prediction of delirium. However, the number of studies in cardiac surgical patients that have used machine learning methods is very limited. Objective This study aimed to explore the application of several machine learning predictive models that can pre-emptively predict delirium in patients undergoing cardiac surgery and compare their performance. Methods We investigated a number of machine learning methods to develop models that can predict delirium after cardiac surgery. A clinical dataset comprising over 5000 actual patients who underwent cardiac surgery in a single center was used to develop the models using logistic regression, artificial neural networks (ANN), support vector machines (SVM), Bayesian belief networks (BBN), naïve Bayesian, random forest, and decision trees. Results Only 507 out of 5584 patients (11.4%) developed delirium. We addressed the underlying class imbalance, using random undersampling, in the training dataset. The final prediction performance was validated on a separate test dataset. Owing to the target class imbalance, several measures were used to evaluate algorithm’s performance for the delirium class on the test dataset. Out of the selected algorithms, the SVM algorithm had the best F1 score for positive cases, kappa, and positive predictive value (40.2%, 29.3%, and 29.7%, respectively) with a P=.01, .03, .02, respectively. The ANN had the best receiver-operator area-under the curve (78.2%; P=.03). The BBN had the best precision-recall area-under the curve for detecting positive cases (30.4%; P=.03). Conclusions Although delirium is inherently complex, preventive measures to mitigate its negative effect can be applied proactively if patients at risk are prospectively identified. Our results highlight 2 important points: (1) addressing class imbalance on the training dataset will augment machine learning model’s performance in identifying patients likely to develop postoperative delirium, and (2) as the prediction of postoperative delirium is difficult because it is multifactorial and has complex pathophysiology, applying machine learning methods (complex or simple) may improve the prediction by revealing hidden patterns, which will lead to cost reduction by prevention of complications and will optimize patients’ outcomes.

Hospital-acquired infections have been suggested to affect patients' outcomes and raise health care costs. However, research regarding the change in rates and types of infections over time remains limited.All patients who underwent cardiac surgical procedures from 1995 to 2012 at the Queen Elizabeth II Health Sciences Center in Halifax, Canada were identified. The prevalence of superficial surgical site infection (sSSI), deep surgical site infection (dSSI), urinary tract infection, sepsis, pneumonia, and leg site infection was examined to determine trends in infections over time. Nonparsimonious logistic regression models were created to identify independent preoperative predictors of length of stay and infection onset.A total of 19,333 consecutive patients underwent cardiac surgical procedures, of whom 2,726 (14%) contracted at least one postoperative infection. The incidence of infections increased from 8% to 20% during the 17-year span (p0.0001). The overall prevalence of infection types, from highest to lowest, was pneumonia (6%), urinary tract infection (6%), sepsis (3%), sSSI (2%), leg infection (2%), and dSSI (1%). After adjusting for clinical differences, postoperative infection was found to be an independent predictor of length of stay longer than 9 days. In turn, independent predictors for contracting a postoperative infection included operative era, advanced age of patients, and complex procedures.The incidence of infection increased nearly threefold since 1995 independent of patient- or procedure-related variables and was found to affect hospital length of stay significantly. Our findings highlight that efforts to monitor only rates of hospital-acquired infections may not in isolation help affect patient care.

The use of 1 or more mediastinal chest tubes has traditionally been routine for all cardiac surgery procedures to deal with bleeding. However, it remains unproven whether multiple chest tubes offer a benefit over a single chest tube.All consecutive patients undergoing cardiac surgery (2005-2010) received at least 1 chest tube at the time of surgery based on surgeon preference. Patients were grouped into those receiving a single chest tube (SCT) and those receiving multiple chest tubes (MCT). The primary outcome was return to the operating room for bleeding or tamponade.A total of 5698 consecutive patients were assigned to 2 groups: 3045 to the SCT and 2653 to the MCT group. Patients in the SCT group were older, more often female and less likely to undergo isolated coronary artery bypass graft than those in the MCT group. Unadjusted outcomes for SCT and MCT, respectively, were return to the operating room for bleeding or tamponade (4.7% v. 5.0%; p = 0.50), intensive care unit stay longer than 48 hours (25.5% v. 27.9%; p = 0.041, postoperative stay9 days (31.5% v. 33.1%; p = 0.20) and mortality (3.8% v. 4.6%; p = 0.16). Logistic regression analysis, adjusted for clinical differences between groups, showed that the number of chest tubes was not associated with return to the operating room for bleeding or tamponade.The use of multiple mediastinal chest tubes after cardiac surgery confers no advantage over a single chest tube in preventing return to the operating room for bleeding or tamponade.De tout temps, lors de chirurgies cardiaques, on a posé 1 ou plusieurs drains thoraciques médiastinaux pour gérer les saignements. Or, il n’a pas été démontré que la pose de plusieurs drains plutôt que d’un seul confère un avantage.On a posé au moins un drain thoracique à tous les patients consécutifs soumis à une chirurgie cardiaque (2005–2010) au moment de l’intervention, selon la préférence des chirurgiens. Les patients ont été regroupés selon qu’on leur avait posé un seul drain thoracique (SDT) ou plusieurs (PDT). Le paramètre principal était le retour au bloc opératoire pour hémorragie ou tamponnade.En tout 5698 patients consécutifs ont été scindés en 2 groupes : 3045 dans le groupe SDT et 2653 dans le groupe PDT. Les patients du groupe SDT étaient plus âgés, plus souvent de sexe féminin et moins susceptibles de subir un pontage aortocoronarien isolé comparativement au groupe PDT. Les paramètres non ajustés pour les groupes SDT et PDT, respectivement, ont été retour au bloc opératoire pour hémorragie ou tamponnade (4,7 % c. 5,0 %;La pose de plusieurs drains thoraciques plutôt que d’un seul après la chirurgie cardiaque ne confère aucun avantage en ce qui concerne le retour au bloc opératoire pour hémorragie ou tamponnade.De tout temps, lors de chirurgies cardiaques, on a posé 1 ou plusieurs drains thoraciques médiastinaux pour gérer les saignements. Or, il n’a pas été démontré que la pose de plusieurs drains plutôt que d’un seul confère un avantage.On a posé au moins un drain thoracique à tous les patients consécutifs soumis à une chirurgie cardiaque (2005–2010) au moment de l’intervention, selon la préférence des chirurgiens. Les patients ont été regroupés selon qu’on leur avait posé un seul drain thoracique (SDT) ou plusieurs (PDT). Le paramètre principal était le retour au bloc opératoire pour hémorragie ou tamponnade.En tout 5698 patients consécutifs ont été scindés en 2 groupes : 3045 dans le groupe SDT et 2653 dans le groupe PDT. Les patients du groupe SDT étaient plus âgés, plus souvent de sexe féminin et moins susceptibles de subir un pontage aortocoronarien isolé comparativement au groupe PDT. Les paramètres non ajustés pour les groupes SDT et PDT, respectivement, ont été retour au bloc opératoire pour hémorragie ou tamponnade (4,7 % c. 5,0 %;La pose de plusieurs drains thoraciques plutôt que d’un seul après la chirurgie cardiaque ne confère aucun avantage en ce qui concerne le retour au bloc opératoire pour hémorragie ou tamponnade.

Background Delirium is a temporary mental disorder that occurs frequently among hospitalized patients. In this study we sought to develop a user-friendly scorecard based on perioperative features to identify patients at risk of developing agitated delirium after cardiac surgery. Methods Retrospective analysis was performed on adult patients undergoing cardiac surgery in a single center. A parsimonious predictive model was created, with subsequent internal validation. Then a simple scorecard was developed that can be used to predict the probability of agitated delirium. Results Among the 5584 patients who met the study criteria, 614 (11.4%) developed postoperative agitated delirium. Independent predictors of postoperative agitated delirium were age, male gender, history of cerebrovascular disease, procedure other than isolated Coronary Arteries Bypass Surgery, transfusion of blood products within the first 48 h, mechanical ventilation for > 24 h, length of stay in the Intensive Care Unit. The scorecard stratified patients into 4 categories at risk of postoperative agitated delirium ranging from 30%. Conclusion Using a large cohort of adult patient's undergoing cardiac surgery, a user-friendly scorecard was developed and validated, which will facilitate the implementation of timely interventions to mitigate adverse effects of agitated delirium in this high risk population.

Purpose Cardiac allograft vasculopathy (CAV) is characterized by adventitial fibrosis, medial remodelling, and intimal expansion. The current etiology of CAV predicts a homogeneous smooth muscle cell (SMC) rich intimal lesion with circumferentially orientated SMC. This paradigm was developed primarily from animal models yet is incongruous with human CAV. Normal human epicardials exhibit a concentric, SMC-rich, benign intimal thickening (BIT) that is lacking in rodents. We propose that retention of BIT after transplant accounts for the donor-derived, SMC-rich nature of human CAV. Methods and Materials Coronary sections were collected at autopsy from patients who fit cardiac donor criteria (n=10) and from cardiac transplant recipients (n=34). Sections were stained with H&E, elastin, and Masson’s trichrome. IHC identified Tcells, macrophages, and alpha-actin. Artery components were measured using digital image analysis. Results No significant difference was found between the mean thickness of the BIT in normal, donor-eligible vessels and the mean thickness of the putative carry-over BIT in transplant recipient vessels. In the majority of vessels (28/34) the intimal lesions contained two definable layers. The lumenal layer had few SMC and many macrophages. In contrast, the layer adjacent to the media had many SMC and few macrophages which is characteristic of donor-derived BIT. Longitudinal sections demonstrated that, like donor BIT, this area had a longitudinal SMC orientation. This suggests that the layer adjacent to the media reflects carryover donor BIT. Vessels harvested at 1, 4, and 10d post transplant confirmed retention of BIT after transplant. Conclusions We propose that retention of the BIT after transplant accounts for the donor-derived, SMC-rich nature of human CAV. We suggest that perturbation of the BIT provides the inflammatory foundation for an accelerated atherosclerosis development in the epicardial coronaries of transplant patients. This expanding accelerated atherosclerosis, along with the underlying BIT, exhibit the characteristics ascribed to CAV.

ObjectivePatients who undergo off-pump coronary artery bypass grafting (OPCAB) commonly receive fewer bypass grafts and are more often incompletely revascularized compared with those receiving conventional coronary artery bypass (CCAB) recipients. Because this can compromise survival, we sought to determine whether patients undergoing OPCAB are incompletely revascularized and whether this affects long-term survival and freedom from cardiac events.MethodsOPCAB cases (n = 411) performed from January 1, 1997 to June 30, 2003 were considered for inclusion and matching with 874 randomly selected, contemporary CCAB cases. After propensity matching, 308 OPCAB cases and 308 CCAB cases were included in the final analysis. We compared the number of bypass grafts and the completeness of revascularization by coronary territory. Survival and readmission for cardiac causes were monitored for up to 10 years postoperatively, with a median follow-up period of 5.9 years.ResultsOn average, the patients undergoing OPCAB received significantly fewer distal anastomoses than did those undergoing CCAB (mean ± standard deviation, 2.6 ± 0.9 vs 3.0 ± 1.0, P

Objectives. Comprehension of risks, benefits, and alternative treatment options has been shown to be poor among patients referred for cardiac interventions. Patients’ values and preferences are rarely explicitly sought. An increasing proportion of frail and older patients are undergoing complex cardiac surgical procedures with increased risk of both mortality and prolonged institutional care. We sought input from patients and caregivers to determine the optimal approach to decision making in this vulnerable patient population. Methods. Focus groups were held with both providers and former patients. Three focus groups were convened for Coronary Artery Bypass Graft (CABG), Valve, or CABG +Valve patients ≥ 70 y old (2-y post-op, ≤ 8-wk post-op, complicated post-op course) (n = 15). Three focus groups were convened for Intermediate Medical Care Unit (IMCU) nurses, Intensive Care Unit (ICU) nurses, surgeons, anesthesiologists and cardiac intensivists (n = 20). We used a semi-structured interview format to ask questions surrounding the informed consent process. Transcribed audio data was analyzed to develop consistent and comprehensive themes. Results. We identified 5 main themes that influence the decision making process: educational barriers, educational facilitators, patient autonomy and perceived autonomy, patient and family expectations of care, and decision making advocates. All themes were influenced by time constraints experienced in the current consent process. Patient groups expressed a desire to receive information earlier in their care to allow time to identify personal values and preferences in developing plans for treatment. Both groups strongly supported a formal approach for shared decision making with a decisional coach to provide information and facilitate communication with the care team. Conclusions. Identifying the barriers and facilitators to patient and caretaker engagement in decision making is a key step in the development of a structured, patient-centered SDM approach. Intervention early in the decision process, the use of individualized decision aids that employ graphic risk presentations, and a dedicated decisional coach were identified by patients and providers as approaches with a high potential for success. The impact of such a formalized shared decision making process in cardiac surgery on decisional quality will need to be formally assessed. Given the trend toward older and frail patients referred for complex cardiac procedures, the need for an effective shared decision making process is compelling.

Late cardiac graft rejection, primarily mediated by allograft vasculopathy (AV), remains a major limitation to cardiac transplantation, even in the face of significant calcineurin inhibitor (CNI) immunosuppression. The role played by alloantibody in AV is unclear. Evidence that CNI immunosuppression suppresses CD4(+) T-cell function would suggest that antibody production and effector function would be severely limited in CNI-treated patients. In this study we examine the capacity of CNI-treated animals to develop effective alloantibody that can mediate AV.Wild-type (WT) B6 mice were alloimmunized using donor splenocytes or a fully major histocompatibility complex-mismatched allogeneic abdominal aortic graft in the presence of CNI immunosuppression (30 or 50 mg/kg/day cyclosporine A). Anti-serum was harvested and tested using complement-dependent in vitro cytotoxicity assays. Anti-serum was passively transferred to immunodeficient RAG1(-/-) recipients of allogeneic grafts. C4d deposition was quantified in the allografts from WT recipients.CNI immunosuppression did not prevent the development of alloantibody in response to either immunization method (p0.05). Passive transfer of anti-serum generated AV lesions in immunodeficient graft recipients and mediated complement-dependent destruction of donor cells (p0.05). C4d deposition was localized to the media of grafts of CNI treated animals.CNI therapy does not prevent the production of alloantibody with the capacity to mediate AV. C4d deposition in the media suggests a role for medial smooth muscle cell loss in antibody-mediated AV lesion development in our model.

Allograft vasculopathy (AV) has emerged as a major obstacle for long-term graft survival after cardiac transplantation. The shortage of donor hearts has meant fewer restrictions have been placed on acceptable hearts over the past few years resulting in an increase in the number of older hearts in the donor pool. This increase has subsequently led to the increase of donor hearts containing pre-existing disease. The importance of this pre-existing donor vascular disease in AV outcomes remains controversial. In this study we address this by taking advantage of the fact that B6 Apolipoprotein-E knockout mice develop atherosclerotic lesions in their aortic tracts that closely model human naturally occurring vascular disease. By using these mice as donors, we transplant known levels of pre-existing disease into fully disparate (C3H) recipients. Cyclosporin A is used to prevent acute rejection and allow for allograft vasculopathy. We found that pre-existing lesions are retained in this model after transplantation and that they contribute to increase in lesion size and to increased lumenal narrowing. The de novo AV lesions overlay the pre-existing lesions and this leads to areas of eccentric lesion formation in the vessels with likely accompanying exacerbation of flow perturbation.

BACKGROUND The aim of this study was to determine the role of alloantibody in the development of cardiac allograft vasculopathy (AV). AV is the main pathologic indicator of chronic cardiac graft rejection resulting in graft loss at 10 years posttransplant. In AV, a neointimal lesion forms resulting in luminal occlusion and damage to the transplanted organ. AV is T-cell mediated, but the role played by B cells and antibody in AV development has been controversial. No studies have been conducted in the presence of a clinically relevant immunosuppressant. In our study, we use cyclosporin A, a calcineurin inhibitor. METHODS Two models of B-cell deficiency were used as recipients of a C3H/HeJ abdominal aortic graft; grafts were harvested at 8 weeks. T- and B-cell immunodeficient mice (RAG1-/-) received passively transferred anti-C3H antibody, raised in B6 mice. Cyclosporin A was administered daily to both control and experimental groups. Alpha-actin staining was used to identify myofibroblasts in the neointima. RESULTS Lesions in B-cell-deficient B6 mice were not significantly different in size from those of control mice. Lesions in both B-cell-deficient and wild-type mice showed similar levels of alpha-actin positivity. Passive transfer of antibody to RAG1-/- mice resulted in small, alpha-actin-positive lesions. CONCLUSIONS B cells are not required for the development of AV, but the presence of an alloantibody can contribute to AV. We hypothesize that the alloantibody mediates AV by initiating complement-mediated killing of smooth muscle cells, based on an in vitro work. Of interest, we found that the neointimal lesions of B-cell-deficient mice and mice that received antibody showed the presence of alpha-actin in myofibroblasts.

BACKGROUND: The Canadian health care system is mandated to provide reasonable access to health care for all Canadians regardless of age, sex, race, socioeconomic status or place of residence. In the present study, the impact of place of residence in Nova Scotia on access to cardiac catheterization and long-term outcomes following an acute myocardial infarction (MI) were examined. METHODS: All patients with an acute MI who were hospitalized between April 1998 and December 2001 were identified. Place of residence was defined by postal code and separated into three categories: metropolitan area (MA); nonmetropolitan urban area (UA); and rural area (RA). Rates of and waiting times for cardiac catheterization were determined, as were risk-adjusted long-term rates of mortality and readmission to the hospital. RESULTS: A total of 7351 patients were hospitalized with an acute MI during the study period. Rates of cardiac catheterization differed across the three groups (MA 45.6%, UA 37.3%, RA 37.3%; P

Immunosuppressive treatments are available to suppress acute cardiac rejection; however, no viable treatment exists for long-term cardiac graft failure. Moreover, extended use of calcineurin inhibitor immunosuppressants, the mainstay of the current therapeutic for cardiac transplantation, leads to significant associated pathologies such as nephrotoxicity and increased risk of cardiac disease. For the last ten years alternatives to calcineurin inhibitors, or adjuvant therapies designed to complement their activities, have been explored. In tandem with this development, there has been considerable interest in Traditional Chinese Medicines (TCM) as sources for novel therapeutics. Our study examines the ability of the TCM Cordyceps sinensis to reduce acute and chronic rejection associated with cardiac transplantation. The objectives of this study were to first determine if oral delivery of the extract could reduce acute rejection in a rat heterotopic heart model of transplantation. The second objective was to determine, in vitro, if a sterile, aqueous extract of C. sinensis could decrease CD8+ T cell activity. The third objective was to determine if oral delivery of the extract could ablate allograft vasculopathy in a mouse abdominal aortic transplant model. We found that oral delivery of the extract demonstrated a reduction in acute rejection when used in conjunction with a sub-therapeutic dose of Cyclosporine. Further, we found, using a mixed lymphocyte reaction, that the extract was able to significantly reduce CD8+ T cell activity. Finally, we demonstrate that oral delivery of the extract, used with a therapeutic dose of Cyclosporine to suppress acute rejection, ablates allograft vasculopathy.

The respective roles of the endothelium and the media as allo-immune targets in the generation of allograft vasculopathy (AV) have yet to be clearly defined. Although endothelial damage has been implicated in the progression of AV, evidence from mechanical vascular injury models suggests that medial injury may play a more dominant role. The overall objective of this research was to determine the relative importance of the endothelium versus the media as a target for immune injury and induction of AV. To investigate this we developed a novel model which involved the creation of chimeric aortic segments. To accomplish this we removed aortic segments from C3H/HeJ (C3H) mice and stripped them of endothelium by a short pulse with EDTA. The stripped C3H grafts were implanted into immunodeficient C57BL/6 (B6) RAG1−/− mice for a period of 21 days. As the immunodeficient mice did not mount an allo-immune response to the grafts, the endothelium was renewed by normal repair mechanisms. The new endothelium was recipient in origin, resulting in a chimeric graft with C3H media and B6 endothelium. We confirmed complete denudement by immunocytochemistry for endothelial specific markers, as well as by transmission and scanning electron microscopy. Replacement of endothelium with recipient endothelial cells was confirmed by immunocytochemistry, electron microscopy and by using a green fluorescent protein mouse transplant combination. Subsequent re-transplantation of the chimeric grafts into either B6 or C3H recipients demonstrated that an allogeneic media is more important than an allogeneic endothelium in inducing robust AV.

We have developed a model of aortic allograft vasculopathy (AV) that uses mouse strains that are fully disparate at Class I, Class II and minor histocompatibility antigens. Acute rejection is ablated with therapeutic doses of the calcineurin inhibitor Cyclosporine A (CyA). In this way we successfully mimic human disease. Using this model we have demonstrated, with cell transfer models using highly purified T cell populations, that calcineurin inhibitors ablate CD4(+) T cell effector mechanisms. As such, in the presence of calcineurin inhibition, graft vasculopathy is dependent on CD8(+) T cell effector mechanisms. In this study we examine the etiology of graft vasculopathy by these CD8(+) T cells in the presence of calcineurin inhibition. We transferred CD8(+) T cells from CyA treated IFN-gamma deficient mice into immunodeficient mouse recipients of aortic allografts to demonstrate that IFN-gamma production by CD8(+) T cells is essential for the development of AV in the presence of calcineurin inhibition. Using two models of CTL ablation we also demonstrated that CTL activity by CD8(+) T cells is essential for the development of AV in the presence of calcineurin inhibition. This is in contrast to models without calcineurin inhibitor immunosuppression where either pathway is capable, by itself, of inducing AV. These data indicate that although calcineurin inhibition ablates CD4(+) T cell effects and weakens CD8(+) T cell pathways, the antigenic challenge of the graft is enough to induce sufficient responsiveness from CD8(+) T cells to induce robust AV.

Background Mitral insufficiency is known to occur in a substantial proportion of patients with heart failure. Its relationship with morbidity and mortality is poorly described. Methods The mortality and hospitalization for heart failure were retrospectively examined in patients who underwent baseline echocardiography in the Studies Of Left Ventricular Dysfunction (SOLVD) treatment and prevention trials. The presence and grade of mitral insufficiency was assessed, and patients with and without mitral insufficiency were compared. Results Patients with left ventricular dysfunction and mitral insufficiency had greater than twofold increased risk of death or admission for heart failure over two years (RR 2.38, 95% CI 1.43 to 3.97). This excess risk persisted after adjustment for the severity of heart failure, etiology and differences in treatment (RR 1.82, 95% CI 1.04 to 3.17; P=0.04). The presence of moderate mitral insufficiency versus no insufficiency was associated with even greater independent risk (RR 2.20, 95% CI 1.01 to 4.80; P=0.05). Results were consistent with binary and ordinal analysis of mitral insufficiency. Conclusion The presence of mitral insufficiency in patients with left ventricular dysfunction is independently associated with adverse outcomes, including death and hospitalization for heart failure. This has potentially important clinical implications for the assessment and management of patients with heart failure.

Background Despite the proposed advantages of off-pump coronary artery bypass graft (CABG) surgery, some controversy remains as to its advantages compared with on-pump CABG. The present study evaluates medium-term outcomes from patients that have been randomized to CABG surgery performed on pump versus off pump. Methods All consecutive patients enrolled into a previously completed randomized trial comparing CABG surgery performed on (n = 150) versus off (n = 150) pump were included. The analysis was performed on an intention-to-treat basis. The outcomes of interest were all-cause mortality and readmission to hospital for cardiac reason. Results The in-hospital outcomes were excellent in both groups with a mortality rate of 0.7% in the on-pump versus 1.3% in the off-pump group ( P = .56). Median follow-up was 3.8 years (interquartile range, 3.4-4.4 years) with 1 patient lost to follow-up (99% complete). There were 12 late deaths, 8 in the off-pump group and 4 in the on-pump group, which were not statistically different between groups ( P = .23) and resulted in a greater than 90% survival at 4 years. Freedom from readmission to hospital for cardiac cause was not statistical different between the 2 groups with 70% event-free survival at 4 years. Multivariate analysis failed to identify the type of procedure (on vs off pump) as an independent predictor of adverse cardiovascular event (mortality + readmission to hospital). Conclusions We have shown that in patients randomized to CABG surgery performed on pump versus off pump, excellent medium-term results can be obtained with either technique. We have been unable to demonstrate that one technique is superior to the other.

Increasingly, patients are being referred for coronary artery bypass grafting (CABG) for management of symptoms after prior percutaneous coronary intervention (PCI). In this study, we assessed the impact of prior PCI on inhospital mortality after CABG.Perioperative data were collected on patients who underwent first-time CABG at 2 surgical centers. Patients who underwent PCI and CABG during the same admission were excluded. Patients with prior PCI were compared with patients with no prior PCI, and the risk-adjusted impact of prior PCI on inhospital mortality after CABG was determined using both multivariate techniques and propensity score matching techniques.Six thousand thirty-two patients met inclusion criteria. Patients with prior PCI were less likely to be between the ages of 70 and 80 (P.0001), to have an ejection fraction0.40 (P.0001), and to have 3-vessel/left main disease (P.0001). They were, however, more likely to have Canadian Cardiovascular Society class IV symptoms (P.0001) and to have an urgent status (P = .02). Rates of inhospital mortality after CABG were higher in patients with prior PCI (3.6% vs 2.3%, P = .02). Using multivariate techniques, prior PCI emerged as an independent predictor of postoperative inhospital mortality (odds ratio 1.93, P = .003). When patients with prior PCI were matched to patients with no prior PCI using propensity scores, inhospital mortality remained higher among patients with prior PCI (3.6% vs 1.7%, P = .01).Patients with prior PCI presented for CABG with less comorbidity and diminished coronary disease; yet, they had more advanced symptoms and greater urgency. After adjusting for these differences, prior PCI emerged as an independent predictor of inhospital mortality after CABG.

Although octogenarians are being referred for coronary artery bypass grafting (CABG) with increasing frequency, contemporary outcomes have not been well described. We examined data from 4 Canadian centres to determine outcomes of CABG in this age group.Data for the years 1996 to 2001 were examined in a comparison of octogenarians with patients less than 80 years of age. Logistic regression analysis was used to adjust for preoperative factors and to generate adjusted rates of mortality and postoperative stroke.A total of 15,070 consecutive patients underwent isolated CABG during the study period. Overall, 725 (4.8%) were 80 years of age or older, the proportion increasing from 3.8% in 1996 to 6.2% in 2001 (p for linear trend = 0.03). The crude rate of death was higher among the octogenarians (9.2% v. 3.8%; p0.001), as was the rate of stroke (4.7% v. 1.6%, p0.001). The octogenarians had a significantly greater burden of comorbid conditions and more urgent presentation at surgery. After adjustment, the octogenarians remained at greater risk for in-hospital death (odds ratio [OR] 2.64, 95% confidence interval [CI] 1.95-3.57) and stroke (OR 3.25, 95% CI 2.15-4.93). Mortality declined over time for both age groups (p for linear trend0.001 for both groups), but the incidence of postoperative stroke did not change (p for linear trend = 0.61 [age80 years] and 0.08 [ageor = 80 years]). Octogenarians who underwent elective surgery had crude and adjusted rates of death (OR 1.31, 95% CI 0.60-2.90) and stroke (OR 1.59, 95% CI 0.57-4.44) that were higher than but not significantly different from those for non-octogenarians who underwent elective surgery.In this study, rates of death and stroke were higher among octogenarians, although the adjusted differences in mortality over time were decreasing. The rate of adverse outcomes in association with elective surgery was similar for older and younger patients.

Objective: Surgical repair of mitral insufficiency is most commonly performed through a left atriotomy via the inter-atrial groove or transatrial (septal) approach. While the dome of the left atrium approach has been described for mitral replacement concerns have been raised about its adequacy for complex repairs. We report our experience with mitral valve repair carried out through the dome of the left atrium, in comparison with more standard approaches. Methods: One hundred and thirty-one consecutive patients undergoing mitral valve repair for regurgitation were reviewed retrospectively between 1995 and 2001. Three groups were created based on their surgical approach: inter-atrial groove group ðn ¼ 43Þ, trans-atrial group ðn ¼ 18Þ, and dome of the left atrium group (between the superior vena cava and the ascending aorta; n ¼ 70). Results: The three groups were similar in terms of pre-operative variables except for significantly older patients in the interatrial groove group ðP , 0:001Þ. The etiology of MR was 24% ischemic (P ¼ ns between groups) and 52% of patients had a concomitant procedure, most commonly coronary artery bypass grafting ðP ¼ nsÞ. Valve repairs were achieved using Carpentier techniques including: ring annuloplasty ðn ¼ 130Þ, isolated posterior leaflet resection ðn ¼ 69Þ, isolated anterior leaflet ðn ¼ 11Þ, or bi-leaflet repair ðn ¼ 19Þ. The overall mortality was 4% with a median length of hospitalization of 7 days and these did not differ significantly between groups. However, longer CPB times ðP , 0:01Þ and requirement for prolonged mechanical ventilation ðP ¼ 0:002Þ were more frequent in the inter-atrial groove group. Conclusion: We report a simple, alternative approach for mitral valve repair via the dome of the left atrium that provides similar outcome to other commonly used approaches. q 2002 Elsevier Science B.V. All rights reserved.

To determine the nature of the proliferative lesion in obliterative airway disease, heterotopic tracheal allograft transplantation was performed between fully disparate Brown Norway and Lewis rat strains. Four weeks after transplantation, the resulting lumenal occlusive lesion was stripped from the underlying tissue. The lesion was probed using immunohistochemical analysis with monoclonal antibodies and for DNA using strain-specific primers for Brown Norway or Lewis major histocompatibility complex Class I alleles. The lesions were alpha-actin positive, and polymerase chain reaction probing revealed only recipient DNA in the lesion tissue, regardless of the direction of transplantation, with no amplification of donor DNA. From this, we conclude that the proliferative lesion in the rat heterotopic tracheal model is of recipient origin a finding with important implications for the pathobiology of obliterative airway disease.

The intraaortic balloon pump (IABP) has been used in cardiac operations since the late 1960s. Over the years, with refinements in technology, its use has expanded; the IABP is now the most commonly used mechanical assist device in cardiac operative procedures. This review provides an evaluation of evidence for the efficacy of IABP use in different clinical scenarios, using the American College of Cardiology/American Heart Association classification of evidence where appropriate. We evaluated complications and outcomes associated with IABP use, and attempted to draw conclusions regarding the use of the IABP in different clinical situations. We examined the trends and variation in utilization over time and across centers. We discussed the IABP in light of new cardiac assist devices and the changing patient population and management strategies. Lastly, we identified areas of future research.

Allospecific memory T cells are a recognized threat to the maintenance of solid-organ transplants. Limited information exists regarding the development of alloreactive memory T cells when post-transplant immunosuppression is present. The clinical practice of delaying calcineurin inhibitor (CNI) initiation post-transplant may permit the development of a de novo allospecific memory population. We investigated the development of de novo allospecific memory CD8+ T cells following the introduction of CNI immunosuppression in a murine model using allogeneic cell priming. Recipient mice alloprimed with splenocytes from fully mismatched donors received cyclosporine (CyA), initiated at 0, 2, 6, or 10days post-prime. Splenocytes from recipients were analyzed by flow cytometry or enzyme-linked immunosorbent assay for evidence of memory cell formation. Memory and effector CD8+ T cell development was prevented when CyA was initiated at 0day or 2days post-prime (p0.001), but not 6days post-prime. Following a boost challenge, these memory CD8+ T cells were capable of producing a similarly sized population of secondary effectors as recipients not treated with CyA (p0.05). Delaying CyA up to 6days or later post-prime permits the development of functional de novo allospecific memory CD8+ T cells. The development of this potentially detrimental T cell population in patients could be prevented by starting CNI immunosuppression early post-transplant.

Objective: Experimental arterial allografts, used as models of chronic rejection, undergo marked loss of smooth muscle cells (SMC) from their media prior to the development of occlusive, intimal proliferative lesions. Medial SMC loss has been described in human heart transplants, and may be related to the development of occlusive coronary lesions which are the hallmark of chronic rejection. This SMC loss does not exhibit the characteristics of necrotic cell death. We sought to determine whether medial SMC loss in arterial allografts occurs by apoptosis. We further investigated these allografts for cytolytic cell-derived inducers of apoptosis, Finally, we compared two different strain combinations to assess the impact of varying histoincompatability on medial SMC loss. Methods: Evidence for internucleosomal DNA degradation, which is characteristic of apoptosis, was sought by the in situ terminal deoxynucleotidyl transferase nick end labelling (TUNEL) method carried out on Lewis to Fisher rat femoral artery transplants (disparate at minor loci only) and Brown Norway to Lewis aortic transplants (fully disparate at major and minor loci). Isografts (Lewis to Lewis) served as controls. In a separate series of experiments graft mRNA was extracted and analysed by reverse transcription-polymerase chain reaction (RT-PCR) with primers for molecular inducers of apoptosis (TNF-a, Fas ligand, perforin, and granzyme-B) which are derived from cytolytic cells known to be present in allografts. Results: Allograft media contained large numbers of TUNEL stained nuclei in both strain combinations. Neither isografts nor ungrafted femoral artery segments stained positive for apoptosis. RT-PCR on whole allografts in both strain combinations revealed sustained upregulation of perforin, granzyme-B, Fas-ligand and TNF-a mRNA concomitant with medial SMC loss. Autografts demonstrated sustained up regulation of TNF-a, and perforin, but only brief upregulation of granzyme-B, and no upregulation of Fas-ligand. Conclusions: These data strongly suggest that medial SMC loss in allograft arteriopathy occurs by apoptosis. Further, RT-PCR data indicate that cytolytic cell-derived inducers of apoptosis are upregulated in these grafts and may be accountable for medial SMC apoptotic cell death. Finally, fully-disparate (Brown Norway to Lewis) and minor-only incompatible (Lewis to Fisher) strain combinations both resulted in marked intimal proliferation, medial SMC loss by apoptosis, and similar patterns of expression of cytolytic cell derived inducers of apoptosis. Insofar as intimal proliferative lesion-formation may be dependent on medial damage (as in arterial-injury models), understanding the mechanism of medial SMC loss may provide a novel therapeutic approach to human cardiac transplant arteriopathy. © 1998 Elsevier Science B.V. All rights reserved

Objectives: A total of 4756 cases of intraaortic balloon pump support have been recorded at the Massachusetts General Hospital since the first clinical insertion for cardiogenic shock in 1968. This report describes the patterns of intraaortic balloon use and associated outcomes over this time period. Methods: A retrospective record review was conducted. Results: Balloon use has increased to more than 300 cases a year at present. The practice of balloon placement for control of ischemia (2453 cases, 11.9% mortality) has become more frequent, whereas support for hemodynamic decompensation (congestive heart failure, hypotension, cardiogenic shock) has been relatively constant (1760 cases, 38.2% mortality). Mean patient age has increased from 54 to 66 years, and mortality has fallen from 41% to 20%. Sixty-five percent (3097/4756) of the total patient population receiving balloon support underwent cardiac surgery. Placement before the operation (2038 patients) was associated with a lower mortality (13.6%) than intraoperative (771 patients, 35.7% mortality) or postoperative use (276 patients, 35.9% mortality). Independent predictors of death with balloon pump support were insertion in the operating room or intensive care unit, transthoracic insertion, age, procedure other than angioplasty or coronary artery bypass, and insertion for cardiogenic shock. Independent predictors of death with intraoperative balloon insertion were age, mitral valve replacement, prolonged cardiopulmonary bypass, urgent or emergency operation, preoperative renal dysfunction, complex ventricular ectopy, right ventricular failure, and emergency reinstitution of cardiopulmonary bypass. Conclusions: Balloons are being used more frequently for control of ischemia in more patients who are elderly with lower mortality. An institutional bias toward preoperative use of the balloon pump appears to be associated with improved outcomes. (J Thorac Cardiovasc Surg 1997;113:758-69)

Background Advances in cardiac surgical care have allowed for successful surgery in high-risk elderly patients. Advances in percutaneous coronary intervention (PCI) techniques and expanded indications for PCI have resulted in a decrease in referrals for coronary artery bypass grafting (CABG). Our objective was to document changes in practice patterns and outcomes in a single tertiary cardiac surgery centre serving a large geographic area. Methods For all cardiac surgery cases performed from 2001-2010 we examined its use, patient clinical characteristics, and outcomes. Frailty was assessed using a measure we have previously demonstrated to be associated with adverse outcomes. Results During the study period, annual case volume decreased by 13%. The number of isolated CABG cases declined, and valve surgery and other complex procedures increased. The proportion of patients aged ≥ 80 years rose from 7%-12%, and the proportion of frail patients increased from 4%-10%. Although unadjusted in-hospital mortality remained relatively unchanged, intensive care unit (ICU) stays and prolonged institutional care increased. Older age and frailty were associated with mortality, prolonged ICU stays, prolonged institutional care, and a composite of mortality and major morbidities. Conclusions Our findings showed a decline in CABG, an increase in more complex operations, and an increase in prolonged ICU stays and prolonged institutional care. The proportion of frail and elderly patients increased over time and these patient groups were at higher risk of adverse postoperative outcomes. Particular attention is required in the decision for surgery and perioperative management of these patients.

Background Women undergoing coronary artery bypass grafting (CABG) are at increased risk for morbidity and mortality. Factors responsible for this observation include smaller coronary size and delayed presentation. To date, no studies have examined the effect of the degree of myocardium at risk (MAR) on the relationship between female sex and adverse postoperative events. Methods Consecutive patients undergoing first-time isolated CABG at a single institution from 2002-2007 were identified. MAR was calculated using the weighted Duke Index and was categorized as low, moderate, or high. Multivariable logistic regression models were created to compare the impact of MAR on adverse clinical events. Results We identified 3741 patients, 3325 (89%) of whom had complete angiographic data. Women (n = 755) were older (P = 0.0001) and presented more often with hypertension (P = 0.0001), diabetes (P = 0.0001), heart failure (P = 0.0001), and an urgent/emergent situation ( P = 0.002). After surgery, women experienced greater rates of adverse events (15.2% vs 9.3 %; P = 0.0001). In a fully adjusted logistic regression model, the nested interaction of sex in MAR showed that women had a significantly greater risk of major adverse cardiovascular events (MACE) when MAR was high (odds ratio [OR], 1.9; 95% confidence interval [CI], 1.3-2.6; P = 0.0004). Greater severity of MAR emerged as an independent predictor of adverse events among women (high: OR, 2.9; 95% CI, 1.2-7.3; moderate: OR, 2.2; 95% CI, 0.8-5.7; low: OR, 1.0), but not among men. Conclusions MAR was independently associated with higher rates of adverse events among women but not in men undergoing CABG. This finding may help explain differences in outcomes seen between women and men after revascularization.

Background Marked variation exists concerning the utilization of percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). The objective of this study was to examine differences in predictors of mode of revascularization across 3 provincial jurisdictions. Methods All patients who underwent PCI and isolated CABG in British Columbia, Alberta, and Nova Scotia between 1996 and 2007 were considered. Age- and sex-standardized rates of PCI and CABG per 100,000 population and PCI to CABG ratios were calculated by year and province. Logistic regression models were constructed to identify independent predictors of mode of revascularization in each province. Results A total of 32,190 and 69,409 patients underwent CABG and PCI, respectively, during the study period. Significant increases in the age- and sex-adjusted PCI to CABG ratios were observed in all 3 provinces, but these ratios differed between provinces. Across all 3 jurisdictions, female sex and diagnosis of acute coronary syndrome favoured increased PCI vs CABG, and increased age, left main, or 3-vessel disease occurring before myocardial infarction, and diabetes favoured lower PCI vs CABG. After adjusting for clinical and angiographic factors, there remained a significant variation in choice of PCI vs CABG between the 3 provinces over time. Conclusions Significant interprovincial variability in PCI to CABG ratios was observed. Though certain patient-related factors predictive of either PCI or CABG were identified, factors beyond clinical presentation played a role in the choice of revascularization approach.

We present the case of a 62-year-old man with infectious endocarditis in a Chiari network. Chiari networks are present in 1.5% to 3% of the population. Although Chiari networks are usually clinically insignificant, they are associated with a number of conditions, including patent foramen ovale, thromboembolism, atrial aneurysm, and cardiac arrhythmias. Although there are rare reports of patients with a Chiari network who had endocarditis develop, this is the first report of a patient who had endocarditis develop solely within a Chiari network.

As the professional society representing cardiac surgeons in Canada, the Canadian Society of Cardiac Surgeons (CSCS) recognizes the importance of maintaining a stable cardiac surgical workforce. The current reactive approach to health human resource management in cardiac surgery is inadequate and may result in significant misalignment of cardiac surgeon supply and demand. The availability of forecasting models and high quality, consistent data on productivity, workload, utilization, and demand is a prerequisite for our profession's capacity to predict and plan for changes in health human resources. The CSCS recognizes that improved workforce management is a key component to providing optimal cardiac surgical care for Canadians in the future and has developed the recommendations in this document as a call to action to interested stakeholders and policymakers to bring substantial improvements to health human resource management in cardiac surgery.

Objective: Many studies have reported higher rates of adverse outcomes in women than men following CABG surgery. To date, the mechanism has not been elucidated. We studied a large group of CABG patients for whom detailed angiographic data were available and investigated the impact of myocardium at risk (MAR) on major adverse cardiac events (MACE) in men and women post-CABG. Methods: For patients undergoing isolated primary CABG, a Duke Index score was calculated from angiographic data. Duke Index is a validated score that quantifies MAR using distribution and severity of coronary artery disease. Categories of MAR were defined as Low, Moderate and High based on number of diseased vessels as well as location of disease, with proximal lesions conferring a higher weight than distal stenoses. The post-CABG outcome was in-hospital MACE (1 or more of mortality, low cardiac output, stroke, MI, sepsis, deep sternal wound infection, ventilation >48 hrs or return to ICU). Logistic regression was used to examine the impact of MAR as a predictor of MACE in women and in men, after adjusting for clinical comorbidities. Results: Of 3744 CABG patients, 70% (2614) had complete angiographic data and were included in the analysis; 23% (607 of 2614) were women. Compared with men, women undergoing CABG had similar Duke Index scores but were older and more likely to have diabetes, hypertension, vascular disease, disabling angina, and require urgent surgery. Completeness of revascularization did not differ between men and women. Prevalence of MACE was higher in women than in men: 19.9% (121 of 607) versus 13.0% (262 of 2007), p=0.0001. In a logistic regression model fully adjusted for comorbidities, there was a significant interaction between female sex and increased MAR as predictors of MACE. In separate logistic regression models for each sex, increasing MAR was an independent predictor of MACE for women (High MAR: OR 3.2, 95% CI 1.4-7.6, Moderate MAR: OR 2.5, 95% CI 1.0-6.2), but not for men (High MAR: OR 1.0, 95% CI 0.6-1.7, Moderate MAR: OR 1.1, 95% CI 0.6-1.8). Conclusions: Myocardium at risk impacts post-CABG outcome differently for women than for men. This novel finding suggests that CABG surgery may not provide the same potential for recovery of ischemic myocardium for women compared with men.

The study aim was to evaluate the hemodynamic performance of the St. Jude Medical Epic Supra bioprosthesis during the early six-month follow up period, and to confirm the safety and efficacy of the valve by collecting details of adverse events and NYHA functional classification.Fifty-seven patients undergoing aortic valve replacement (AVR) with the Epic Supra valve between September 2007 and January 2009 at three centers in Canada were evaluated for the study. The subjects were monitored preoperatively, at discharge, and at six months postoperatively. Echocardiographic data were available from 50 subjects at the six-month follow up. In order to prevent observer variability, all echocardiograms were sent to an independent Echocardiography Core Laboratory (ECL) for interpretation of the data.The mean subject age was 74 years. Concomitant coronary artery bypass grafting (CABG) was performed in 44% of the procedures. The mean pressure gradients were 11.2, 12.5, 10.8, 8.4 and 11.3 mmHg, respectively, for valves sized 19 mm (n = 2), 21 mm (n = 20), 23 mm (n = 22), 25 mm (n = 5) and 27 mm (n = 1). The average effective orifice areas (EOAs) were 1.44, 1.57, 1.69, 1.93 and 1.81 cm2 for the .valves sized 19, 21, 23, 25 and 27 mm, respectively.The results of the six-month echocardiographic follow up indicated that the Epic Supra valve offered excellent hemodynamic performance in the 21, 23 and 25 mm sizes. However, additional data are still required for the 19 and 27 mm valves to characterize their performance. The mean gradients and EOA-values were comparable to those of other supra-annular stented tissue valves. The EOA index indicated an absence of prosthesis-patient mismatch, with values in all subjects at or near 0.85 cm2/m2. The percentage of subjects without aortic insufficiency (AI) at follow up was 92%; only four subjects showed trivial AI.

Objectives: Sequential anastomoses in coronary artery bypass grafting (CABG) offer theoretical advantages including increased graft flow and more complete revascularisation. However, published studies concerning the safety and efficacy of this technique are not definitive. The objective of this study was to assess the effect of sequential anastomoses on outcomes following CABG. Methods: Perioperative data were prospectively collected on all patients with triple-vessel disease who underwent first-time, isolated, on-pump CABG between 1995 and 2005 at a single centre. Patients with a left internal mammary artery graft to the anterior wall and saphenous vein grafts to the lateral and posterior walls were included. Results: Compared to patients without sequential anastomoses (n = 1108), patients with sequential anastomoses (n = 1246) were more likely to have an ejection fraction (EF) < 40% (14.9% vs 10.8%, p = 0.004), a recent myocardial infarction (19.3% vs 14.3%, p = 0.001) and an urgent/emergent operative status (19.6% vs 14.4%, p = 0.0008). Median follow-up was 78 months. After adjusting for clinical covariates, sequential grafting was not an independent predictor of in-hospital adverse events (odds ratio (OR) 1.15, 95% confidence interval (CI) 0.88—1.50, p = 0.31) or long-term mortality and/or readmission to hospital (hazard ratio (HR) 0.98, 95% CI 0.86—1.12, p = 0.74). Sequential grafting was an independent predictor of receiving greater than three distal anastomoses (OR 9.26, 95% CI; 6.27—13.67, p < 0.0001). Conclusions: Patients undergoing sequential grafting presented with greater acuity and worse systolic function. After adjusting for baseline differences, sequential grafting was not found to be an independent predictor of adverse events. These results support the safety of sequential anastomoses in patients undergoing CABG. # 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.

Background Percutaneous coronary intervention (PCI) is increasingly being offered to patients with coronary artery disease. The purpose of this study was to determine the impact of this change in coronary revascularization strategy on PCI and coronary artery bypass grafting (CABG) utilization across Canada. Methods All cases of PCI and isolated CABG between years 1994 and 2005 were identified through the Canadian Institute for Health Information. Age- and sex-standardized rates of PCI and CABG per 100,000 population as well as PCI-toCABG ratios were calculated by year and province and across age, sex, income, diabetes, and recent acute coronary syndrome subgroups. In addition, risk-adjusted rates of in-hospital mortality after PCI and CABG were reported by year. Results Between 1994 and 2005, PCI rates increased from 85.6/100,000 to 186.7/100,000 (P b .001), whereas CABG rates remained stable (75.6/100,000-70.8/100,000; P = .43), resulting in an increase in PCI-to-CABG ratio (1.132.64; P b .001). Significant increases in PCI-to-CABG ratios were seen across all provinces (except Newfoundland and Alberta), as well as across all age, sex, income, diabetes, and recent acute coronary syndrome categories. Decline in riskadjusted in-hospital mortality was seen after both CABG (3.9%-2.2%; P b .001) and PCI (1.6%-1.3%; P b .001) but appeared larger after CABG. Conclusions Since 1994, rates of PCI have increased significantly as compared to CABG. During the same period, greater declines in risk-adjusted rates of in-hospital mortality were seen among CABG versus PCI patients. Further study is needed to determine the appropriateness of PCI and CABG rates in terms of clinical outcomes and resource utilization. (Am Heart J 2010;160:958-65.)

Background Endoscopic saphenous vein harvest (EVH) decreases leg wound infections and improves cosmesis after coronary artery bypass grafting (CABG). Recent data, however, suggest that EVH may be associated with reduced graft patency rates. The objective of this study is to assess the effect of EVH on short-term and midterm outcomes after CABG. Methods Data were prospectively collected on all first-time isolated CABG and combined valve/CABG with saphenous vein graft between 1998 and 2007 at a single center. Patients having traditional "open" vein harvest (OVH) were compared with patients having EVH. Multivariate models were used to examine the risk-adjusted impact of EVH on postoperative leg infection, composite in-hospital adverse events, and individual and composite midterm adverse events. Results The study included 5,825 patients, of whom 2,004 (34.4%) had EVH. Patients having EVH were more likely to have ejection fraction less than 50% (32.0% versus 29.3%, p = 0.04), recent myocardial infarction (24.2% versus 18.3%, p p = 0.0009). Median follow-up was 2.6 years. After risk adjustment, EVH was associated with reduced rates of leg infection (odds ratio 0.48, p = 0.003) but had no association with either in-hospital (odds ratio 0.93, p = 0.56) or midterm adverse outcomes (hazard ratio 0.93, p = 0.22). Endoscopic saphenous vein harvest was associated with reduced readmission to hospital for unstable angina (odds ratio 0.74, p = 0.01). Conclusions Endoscopic saphenous vein harvest is associated with a lower rate of leg infection and is not an independent predictor of in-hospital or midterm adverse outcomes. Endoscopic saphenous vein harvest is a safe alternative to OVH for patients undergoing CABG with saphenous vein.

Using a clinically relevant, fully disparate, allogeneic aortic transplant mouse model of allograft vasculopathy, we have demonstrated that neointimal proliferation is dependent on CD8(+) T cell effector pathways in the presence of therapeutic doses of calcineurin inhibitor (CNI) immunosuppression. CD4(+) T cell pathways are ablated by CNI immunosuppression. In the current study, we examined the relationship between CD8(+) T cell activities, medial SMC loss and neointimal hyperplasia. We demonstrate that at 5-6wk post transplantation in a wild type/wild type transplant CD8(+) T cell infiltration, CD8(+) CTL effector cell mediator expression and medial SMC loss all occur within aortic interposition grafts in the face of CNI immunosuppression. Both IFN-gamma and CTL mediated effector function is required for SMC loss and lesion formation under these conditions. Using strain combinations and reconstitution models, we provide data that blockade of the perforin/granzyme pathway does not prevent lesion formation but that blockade of the Fas/FasL pathway of cytotoxicity dramatically reduces SMC loss and prevents neointimal lesion formation. Both of these blockade strategies are in the face of an active IFN-gamma pathway. These data suggest a cooperative role between Fas/FasL and IFN-gamma mediated effector functions in medial SMC loss and neointimal lesion formation.

Patients referred for cardiac surgery are increasingly older, but chronological age does not always capture biological age. This study assessed frailty, as a functional parameter of biological age, as a predictor of mortality or prolonged institutional care. Functional measures of frailty and clinical preoperative data were collected for all cardiac surgery patients at a single center (2004 –2007). Based on the Katz Index of Activities of Daily Living, frailty was defined as any impairment in feeding, bathing, dressing, transferring, toileting, continence, or ambulation, or dementia. The impact of frailty on in-hospital mortality or institutional discharge (other hospital or nursing facility) was assessed with multivariate logistic regression. The interaction of frailty and age was examined, with non-frail patients age Results: Of 3096 patients, 133 (4.3%) were frail. Frail patients were older, more likely to be female, have COPD, CHF, EF

Background— We investigated the association between trainees performing supervised operations and late outcomes of patients undergoing cardiac surgery. Methods and Results— Data were prospectively collected on patients who underwent coronary artery bypass graft surgery, aortic valve replacement, or a combination of these between 1998 and 2005 at the Maritime Heart Center, Halifax, Canada. In-hospital mortality and a composite outcome of in-hospital mortality, stroke, bleeding, intra-aortic balloon pump insertion, renal failure, and sternal infection was compared between teaching (n=1054) and nonteaching cases (n=5877). Late survival and cardiovascular hospital readmissions were also examined. To adjust for baseline risk disparities, we used logistic regression for dichotomous in-hospital outcomes and Cox proportional hazards regression for survival data. Resident cases were significantly more likely to have high-risk features such as depressed ventricular function, redo operation, and urgent or emergent procedure. Resident as primary operator was not independently associated with in-hospital mortality (OR, 1.09; 95% CI, 0.75 to 1.58; P =0.66) or with the composite outcome (OR, 1.01; 95%, CI 0.82 to 1.26; P =0.90). The Kaplan-Meier event-free survival of the 2 groups was equivalent at 1, 3, and 5 years (log-rank P =0.06). By Cox regression, resident cases were not associated with late death or cardiovascular rehospitalization (hazard ratio, 1.05; 95% CI, 0.94 to 1.17; P =0.42). Conclusions— Cases performed by senior-level cardiac surgery residents were more likely to have greater acuity and complexity than staff surgeon-performed cases. However, clinical outcomes were similar in the short- and long-term. Allowing residents to perform cardiac surgery is not associated with adverse patient outcomes.

The cardiopulmonary bypass (CPB) has allowed the establishment of coronary artery bypass graft surgery (CABG) to be a safe and effective treatment for patients with ischemic heart disease. However, the concern that CPB may be responsible for CABG-related morbidity has been raised, and it has been suggested that CABG itself would be safer without CPB. The development of commercially available cardiac stabilization devices resulted in several large, nonrandomized retrospective case series. The studies demonstrated that CABG can be performed safely without CPB (off-pump surgery), and suggested that there are benefits compared with conventional CABG. However, the randomized controlled studies published to date have been, as a whole, unable to conclusively demonstrate advantages of off-pump CABG. The results of these randomized studies are likely responsible for the failure of off-pump CABG to become established as the standard of care.

We investigated the role of CD4 + T cells and CD8 + T cells in mediating allograft vasculopathy in Cyclosporin A (CyA) immunosuppressed mice. We first established that a dose of 50 mg/kg/d CyA was required to prevent acute rejection in C57BL/6 mice. CyA given at 50 mg/kg/d did not prevent allograft vasculopathy in either cardiac or aortic transplants in these mice. Using CD4 −/− and CD8 −/− mice, we established that CyA immunosuppression at this dose was only effective at preventing allograft vasculopathy in mice lacking CD8 + T cells. This implicates CD8 + T cells in the development of AV in situations of clinical cardiac transplantation where CyA is still the mainstay of immunosuppressive therapy. We confirmed the important role for CD8 + T cells in AV in the face of CyA immunosuppression by allopriming mice in the presence of CyA and transferring alloprimed T cells into RAG1 −/− immunodeficient mice. The RAG1 −/− mice were also treated with CyA. In this situation (CyA present during the allopriming and in the recipient), only primed CD8 + T cells could mediate AV, primed CD4 + T cells could not. Alloprimed CD8 + T cells raised in the presence of CyA exhibited markedly reduced direct recognition responses (as measured by MLR) and effector responses (as measured by cytotoxic activity). In contrast indirect activation was retained. We interpret these data to suggest that in the face of CyA immunosuppression CD4 + T cell effector function is ablated while CD8 + T cell function remains partially intact. The in vitro data suggest that the indirect pathway remains intact in this population of CyA resistant CD8 + T cells.

Objective: Recent developments in cardiac stabilization devices, have made OPCAB feasible. However, there is conflicting evidence to date regarding the rate and adverse events associated with conversion from OPCAB to CABG with CPB. The objective of the present study was to review all conversions in the setting of a randomized controlled trial comparing CABG with or without CPB. Methods: Three hundred patients requiring CABG surgery at a single institution were prospectively randomized to have the procedure performed with CPB (n=150) or OPCAB (n=150). Patients that could not be performed OPCAB were defined as conversion group (cross over). Results:Twenty patients were converted from OPCAB to CABG with CPB because of hemodynamic instability (14/20), small target vessel (5/20), or inadequate visualization (1/20). Seventeen were converted during attempts at coronary anastomosis: LAD/diagonal (7/20), circumflex (8/20), or right coronary (2/20). The overall in hospital mortality rate for the trial was 1% but was significantly higher in converted patients (10 vs. 0%; P=0.01). Converted patients required significantly more inotropes (P=0.001) and blood transfusions (P=0.05). An elevated BMI was the only pre-operative variable that appeared to be associated with conversion. Conclusions: In the setting of a randomized controlled trial the overall conversion rate associated with OPCAB reached 13% and was associated with an increased risk of mortality.

Objective : Allograft vasculopathy (AV) has emerged as the major obstacle to long-term survival in clinical heart transplantation. Immune events are implicated in the development of AV, but the cellular and molecular mechanisms involved remain unclear. We sought to determine whether and by what mechanism CD8+ T lymphocytes are able to generate AV in a murine aortic allograft model. Methods : Allo-primed CD8+ T lymphocytes were transferred into immunodeficient (RAG-1−/−) mouse recipients of aortic allografts. We also transferred primed CD8+ T cells with targeted deletions of effector molecules (perforin, Fas-ligand) to determine the role of direct cytolysis (CTL) in CD8+ T-cell-mediated AV. We determined the role of non-CTL effector mechanisms through the transfer of either wildtype or interferon-γ (IFN-γ)-deficient CD8+ T cells into RAG-1−/− recipients of MHC class I-deficient allografts. Results : Adoptive transfer of primed wildtype CD8+ T lymphocytes into immunodeficient recipients of aortic allografts resulted in the development of robust AV lesions. Transfer of CD8+ T lymphocytes with targeted deletions in CTL effector molecules resulted in reduction of AV lesion size but not abrogation. Transfer of wildtype CD8+ T cells into recipients of MHC class I-deficient grafts resulted in a reduction in AV lesion size, while transfer of interferon-γ-deficient CD8+ T cells into MHC class I-deficient grafts abrogated AV. Conclusions : These data indicate that CD8+ T cells mediate AV through direct cytolysis and a distinct interferon-γ-dependent non-CTL effector pathway. Given the resistance of this cell type to conventional immunosuppression, these results may have important therapeutic implications.